1. Field of the Invention
The invention involves a method and apparatus for determining the density or specific gravity of a fluid. More particularly, the present invention relates to the determination of hemoglobin concentration in blood using a specific gravity method and apparatus.
2. Description of the Related Art
The measurement of density and specific gravity has application in many areas of Science, Engineering, Manufacturing, and Quality Assurance. Applications range from indirect measurement of the concentration of analytes in biological fluids, such as blood, saliva, and urine, to using the measurement of specific gravity or density to monitor the process quality of products such as foods, beverages, cosmetics, soaps, paints, and pigments. The measurement of density or specific gravity is also used indirectly to determine other process units such as alcohol degree, milk degree, Brix and API density in product processes.
The measurement of the density or specific gravity of fluids is important, and sometimes critical, for medical analysis and treatment. The density of a fluid is related to several physical properties of the fluid, including its specific gravity which is defined as the ratio of the density of the particular fluid to the density of water. For example, various body fluids, such as blood, urine, or cranial fluid, can be analyzed for their specific gravity to determine other pertinent physical properties. Thus, the analyte concentration of blood can be measured using its specific gravity to determine the amount of hemoglobin in blood or protein in the serum.
Several constraints complicate the measurement of specific gravity of body fluids. One constraint involves the difficulty or discomfort associated with obtaining the body fluid samples. Another constraint involves the criticality of the accuracy of the analyte concentration determination, because physicians select treatments for individuals based on the determined analyte concentrations. A further constraint involves the limited amount of body fluid which may be safely extracted from an individual. These and other constraints require that the measurement be accurate while only needing a small sample.
Conventional methods for measuring density or specific gravity use many different technologies. A common technology involves the manual manipulation of hydrometers, picnometers, and density determination kits using precise weight measurements. Digital density meters are also known to use either refractive index measurement or natural oscillation measurement technology.
Another known method of measuring specific gravity involves measuring the time of fall of a drop of fluid as it falls a fixed distance between two positions through another fluid of known specific gravity, which is termed the "falling drop" method. The "falling drop" method has thus far only received limited application due to the necessity to control the volume of the drop in order to obtain accurate specific gravity measurements. The drop must be non-miscible with the fluid medium, that fluid medium having a relatively low viscosity and a specific gravity lower than that of the drop. The drop must have a precisely dispensed volume which is introduced into the fluid medium below its surface. The non-miscible fluid being measured tends to form a drop in the form of a sphere. The descent of the drop through the fluid medium over a measured distance may be timed by a clinician. Automatic systems are also known which have two photosensors connected to a microprocessor with a timer so that the time of fall between the two sensors may be measured and calibrated against measurements of known specific gravity solutions.
The velocity or rate of fall of the spherical drop through the fluid medium is a function of the specific gravities of the drop and fluid medium, the viscosity of the fluid medium, the size of the drop, and the diameter of the tube containing the fluid medium. For a drop of approximately 35 microliters at terminal velocity in a 16 mm tube, time and distance are used in the following equation to calculate the specific gravity of the fluid: ##EQU1## where SG.sub.f is the specific gravity of the drop, SG.sub.m is the specific gravity of the fluid medium, SG.sub.f is the difference in specific gravity between the drop and the fluid medium, (visc) is the viscosity of the fluid medium, K.sub.1 is a constant related to physical properties of the drop, tube diameter, and fluid medium, K.sub.2 is 2/3 .pi., d is the diameter of the drop, D is the distance of fall through which the drop was timed, and T is the time the drop took to fall through the fluid medium over the predetermined distance. The disadvantage of this "between sensor falling drop" method of specific gravity measurement is that the measured specific gravity is inversely proportional to the diameter or size of the drop. Hence, it is necessary to dispense a precise size drop (volume of sample) to obtain accurate specific gravity measurement.
Although a precise performance of the "between sensor falling drop" method provides an accurate measurement of specific gravity, many difficulties are encountered in precisely performing the required measurements. One difficulty involves the precision of the volume of the drop being measured, because the volume is directly related to the diameter. As the diameter of the drop is a component of the specific gravity calculation above, the volume of the drop must be carefully controlled by dispensing the drop via a pipette under the surface of the fluid medium.
It is difficult and inconvenient for an analyst to dispense precise volumes. In the industrial setting, vibration and other factors may interfere with precise measurements. In the medical setting, the technicians may not have extensive training in precisely measuring the sample fluid. In addition, dispensing the drop under the surface of the fluid medium may result in trapped air bubbles which interferes with the accurate measurement of density or specific gravity. Another problem in dispensing under the fluid surface is that any electrostatic charge on the pipette tip is transferred to the oil and drop, and the charge on the materials thus effects the velocity and direction of the falling drop. This changes the drop fall time and can create errors in the density or specific gravity measurement. Also, conventional low cost transfer pipettes cannot consistently dispense a precise amount of fluid, and the size of the drop may vary from less than 20 microliters to as much as 50 microliters or more. This variability creates a corresponding variability in the specific gravity measurement.
What is needed is a density or specific gravity measurement method and apparatus which eliminates the variability of the measurements.
Also needed is a density or specific gravity measurement method and apparatus which allows for the sample to be dispensed conveniently above the fluid medium's surface.